Spike glycoprotein receptor-binding domain–Angiotensin-converting enzyme 2 complex (SARS-CoV-2 RBD–ACE2 complex)

The SARS-CoV-2-RBD-ACE2 complex is formed when the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein engages ACE2, a membrane-bound enzyme highly expressed in human respiratory, cardiovascular, and other tissues[1][3][5][6]. This interaction is the critical molecular event that mediates viral attachment and entry into host cells, triggering subsequent membrane fusion and cell infection. Structural studies have mapped the key amino acid residues participating in this high-affinity binding, with variant-specific changes enhancing or modifying the interaction (e.g., N501Y in Alpha, T478K/L452R in Delta, multiple mutations in Omicron)[2][4][5][6]. The complex is the principal target for neutralizing antibodies, vaccine-induced immune responses, and therapeutic inhibitors[2][6]. The variability of RBD through mutations underlies the emergence and pathogenicity of variants of concern, while the physiological importance of ACE2 presents unique challenges in drug targeting due to its role in regulating cardiovascular and renal function[1][3].

Other names

SARS-CoV-2 spike RBD–ACE2 complexSARS-CoV-2 S protein RBD–ACE2 complexSpike–ACE2 complexS-RBD–ACE2 complex

Competitive inhibition of RBD binding to ACE2 (neutralizing antibodies); ACE2 decoy binding (soluble ACE2); Allosteric inhibition of the spike protein conformational changes